Karathanou, KonstantinaLazaratos, MichalisBertalan, ÉvaSiemers, MalteBuzar, KrzysztofSchertler, Gebhard F.X.del Val, CoralBondar, Ana-Nicoleta2020-12-042020-12-042020-09-10Karathanou K, Lazaratos M, Bertalan É, Siemers M, Buzar K, Schertler GFX. A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2. J Struct Biol. 2020 Nov 1;212(2):107617.1047-8477http://hdl.handle.net/10668/3218Corona virus spike protein S is a large homo-trimeric protein anchored in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, and contribute symmetrically to a relatively large H-bond cluster at the receptor binding domain, and to a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.enBimolecular structureHydrogen bondingDynamic hydrogen-bond clustersConformational plasticitySARS-CoV-2 protein SACE2Enlace de hidrógenoMedical Subject Headings::Information Science::Information Science::Computing Methodologies::AlgorithmsMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational BiologyMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Physicochemical Processes::Hydrogen BondingMedical Subject Headings::Information Science::Information Science::Computing Methodologies::Computer GraphicsMedical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus InfectionsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, MolecularMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::PandemicsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Dipeptidyl-Peptidases and Tripeptidyl-Peptidases::Peptidyl-Dipeptidase AMedical Subject Headings::Diseases::Virus Diseases::Pneumonia, ViralMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein BindingMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation::Protein Structure, Tertiary::Protein Interaction Domains and MotifsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Molecular Probe Techniques::Protein Interaction MappingMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Metabolic Networks and Pathways::Protein Interaction MapsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation::Protein Structure, QuaternaryMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation::Protein Structure, SecondaryMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Fusion Proteins::Viral Fusion Proteins::Spike Glycoprotein, CoronavirusMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Virus Internalizationresearch article32919067Acceso abierto10.1016/j.jsb.2020.107617PMC7481144